GROWTH MODULATION OF RAF ASSOCIATED TUMORS

缺陷型逆转录病毒中v-raf-1癌基因的鉴定 3611-MSV允许分离一个新的原癌基因家族。 的 v-raf的活性同源物c-raf-1位于染色体上p25位置 3在人类中，在各种瘤形成中经常改变的部位， 包括小细胞肺癌。 此外，将 c-raf-1已经在人胃癌和胶质母细胞瘤中被鉴定。 c-raf-1 mRNA和蛋白在人肺癌细胞系中的表达 其水平超过NIH 3 T3细胞中发现的水平 通过c-raf MSV转化。 研究raf在肺癌发生中的作用 在体内，我们已经开发了一种动物模型，其中90%的新生小鼠 经胎盘用乙基亚硝基脲治疗，出生时用 丁羟甲苯在5 - 14天内会发展成肺肿瘤和淋巴瘤 周 c-raf-1在肿瘤和已建立的细胞系中的高表达， 通过北方印迹和免疫印迹分析确定。 制备的DNA 从肺肿瘤和淋巴瘤中提取的细胞转化为NIH 3 T3细胞， 通过DNA转染测定。 活化转化的本质 目前正在进行DNA检测。 此外，我们现在已经定义了 使用生长调节剂和激素来差异性抑制 raf转化但未转化的体外对照细胞系。 这些 目前正在我们的动物模型系统中测试方案， 使用纯化的raf蛋白进行疫苗接种实验，以检测它们的 对这些肿瘤发展的潜在抑制作用。

The identification of the v-raf-1 oncogene from the defective retrovirus 3611-MSV has allowed the isolation of a new family of proto-oncogenes. The active homolog of v-raf, c-raf-1, is located at position p25 on chromosome 3 in man, a site that is frequently altered in a variety of neoplasia, including small cell lung carcinoma. Moreover, transforming versions of c-raf-1 have been identified in human stomach cancer and glioblastoma. Expression of c-raf-1 mRNA and protein in human lung carcinoma cell lines occurs at levels that are in excess of those found in NIH 3T3 cells transformed by c-raf MSV. To study the role of raf in lung carcinogenesis in vivo, we have developed an animal model where 90% of newborn mice treated transplacentally with ethylnitrosourea and promoted at birth with butylated hydroxytoluene develop lung tumors and lymphomas within 5 to 14 weeks. High c-raf-1 expression in tumors and established cell lines has been determined by Northern blot and immunoblotting analyses. DNA prepared from both lung tumors and lymphomas is transforming for NIH 3T3 cells as determined by DNA-transfection. The nature of the activated transforming DNA is currently being examined. Moreover, we have now defined conditions using growth modulators and hormones for the differential inhibition of raf-transformed, but not untransformed, control cell lines in vitro. These regimens are now being tested in our animal model system, in conjunction with vaccination experiments using purified raf protein, to examine their potential inhibitory actions on the development of these tumors.